| Features: Insect poisoning, anti-cancer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deguelin is a natural compound of isoflavonoid-derived rotenoid isolated from several plant species, including Derris trifoliata Lour and Mundulea sericea (Leguminosae) (4) Deguelin’s ability to modulate multiple signaling pathways—including PI3K/Akt, mTOR, NF-κB, HIF-1α, and MAPK While preclinical studies have utilized dosages in the approximate range of 4–8 mg/kg in animal models, these figures are specific to the experimental conditions and species used in those studies. Deguelin is a rotenoid (isoflavonoid-like botanical insecticide class) found in some Lonchocarpus / Derris species. In cancer literature it’s most often described as a mitochondrial Complex I inhibitor with downstream energy stress + survival pathway suppression (Akt/PI3K, NF-κB) and apoptosis/autophagy induction. A major caution is neurotoxicity signal: rotenoids (including deguelin) have been used in Parkinson’s disease animal models via Complex I inhibition. - Active identity: Rotenoid (deguelin) — a potent mitochondrial Complex I inhibitor with downstream energy-stress signaling (AMPK/mTOR), survival pathway suppression (Akt, NF-κB), and apoptosis/autophagy induction in cancer models; higher caution category due to rotenoid neurotoxicity signals in animal models. Deguelin — a naturally occurring rotenoid derived principally from leguminous plants in the Derris, Lonchocarpus, Tephrosia, and related genera. It is a lipophilic isoflavonoid-related botanical insecticide and experimental anticancer small molecule, commonly abbreviated Deg. Its functional identity is dominated by mitochondrial respiratory Complex I inhibition, with secondary suppression of Hsp90-dependent oncogenic proteins and PI3K/AKT, NF-κB, mTOR, HIF-1α, angiogenic, and metastatic signaling. Deguelin is not an approved anticancer drug and has a substantial translational safety concern because systemic exposure can injure dopaminergic neurons and produce Parkinsonism-like pathology in animals. Primary mechanisms (ranked):
Bioavailability / PK relevance: Deguelin is highly lipophilic and poorly suited to simple aqueous delivery. Rat pharmacokinetic studies found measurable systemic persistence and a relatively long plasma residence time, but human pharmacokinetics, oral bioavailability, therapeutic exposure targets, metabolism, and safe dosing have not been established. Formulation research has therefore focused on analogues, nanoparticles, and other delivery systems intended to improve solubility or tumor exposure. Enhanced delivery could also increase neurological and systemic toxicity. In-vitro vs systemic exposure relevance: Anticancer effects are frequently reported from low-nanomolar to several-micromolar concentrations, depending on the cell model and endpoint. Some sensitive models respond below 0.1 µM, whereas apoptosis, ROS, autophagy, or broad cytotoxicity studies commonly use approximately 1–20 µM. There is no validated human exposure range demonstrating that these concentrations can be achieved safely. Because mitochondrial Complex I inhibition occurs in normal as well as malignant tissue, systemic exposure cannot be assumed to preserve cancer selectivity. Clinical evidence status: Preclinical only. Evidence consists primarily of biochemical studies, cancer-cell experiments, xenografts, chemically induced tumor models, and rodent metastasis or chemoprevention studies. No established human anticancer trial evidence, approved indication, clinically validated dose, or accepted adjunct regimen was identified. Neurotoxicity and delivery limitations currently outweigh the strength of the efficacy evidence for clinical translation. Deguelin Mechanistic Profile
P: 0–30 min R: 30 min–3 hr G: >3 hr |
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| Destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis. Mitochondria are organelles within eukaryotic cells that produce adenosine triphosphate (ATP), the main energy molecule used by the cell. For this reason, the mitochondrion is sometimes referred to as “the powerhouse of the cell”. Mitochondria produce ATP through process of cellular respiration—specifically, aerobic respiration, which requires oxygen. The citric acid cycle, or Krebs cycle, takes place in the mitochondria. The mitochondrial membrane potential is widely used in assessing mitochondrial function as it relates to the mitochondrial capacity of ATP generation by oxidative phosphorylation. The mitochondrial membrane potential is a reliable indicator of mitochondrial health. In cancer cells, ΔΨm is often decreased, which can lead to changes in cellular metabolism, increased glycolysis, increased reactive oxygen species (ROS) production, and altered cell death pathways. The membrane of malignant mitochondria is hyperpolarized (−220 mV) in comparison to their healthy counterparts (−160 mV), which facilitates the penetration of positively charged molecules to the cancer cells mitochondria. The MMP is a critical indicator of mitochondrial function, directly reflecting the organelle's capacity to generate ATP through oxidative phosphorylation. |
| 6669- | Deg, | Mitochondrial Complex I Inhibitors Expose a Vulnerability for Selective Killing of Pten-Null Cells |
| - | vitro+vivo, | Pca, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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